The project is divided into four main specific aims and sections. These are: (1) Experiments to determine whether nerve growth factor (NGF) or NGF-like (i.e. immunologically cross-reactive with mouse NGF or derived from an mRNA that bears sequence homology to that of mouse NGF) molecules are present in the brain. This will be done by Northern- and Western-blot analyses using a cDNA probe for NGF and antibody to NGF. If such material is detected, it will be analyzed by amino acid sequencing. Material detected by Northerns would be cloned by one of several alternative techniques. (2) Levels of mRNA for NGF or NGF-like molecules will be measured (using appropriate cDNA probes) in various regions of postmortem human brains. Such findings will be correlated with any known pathologies of the material. Animal models will also be studied for changes in mRNA levels for NGF or NGF-like molecules in various brain regions as a function of aging and possible pathology. (3) cDNA and antibody reagents will be derived for pituitary fibroblast growth factor (FGF). These tools will be used to study protein and mRNA levels for FGF in various brain regions during aging and in pathological conditions (especially Alzheimer disease). (4) Guidance will be provided for the purification and characterization of the ciliary neuron neuronotrophic factor.